Genetic and metabolic contributions of articular chondrocytes to degenerative joint disease and disturbed skeletal growth that cannot be readily studied using whole cartilage, will be approached by cell culture methods. We propose to carry forward our previous studies of acid mucopolysaccharide and collagen synthesis and extend them to link protein formation. Valid methods for obtaining sulfated mucopolysaccharides in vitro have been developed for rabbit chondrocytes; comparable conditions for human cells are to be worked out. The collagen produced by the chondrocytes under monolayer conditions is of (alpha 1) alpha 2 rather than (alpha 1)3 type. In view of the enormous increase in chondroid expression of ground substance synthesis following switch from monolayer to spinner culture, the molecular species of collagen under these conditions will be re-examined. If an (alpha 1)3 pattern develops, further identification of the collagen will be made. The methods will be applied to joint cartilage from human surgical specimens and also to rabbits and other species having defined inherited cartilage defects such as the achondroplasias resembling the human disorders. The human cells are to be examined for differences according to strata within the cartilage, age effects, osteoarthritis and such genetic disorders as become available. The mechanism of a glycoprotein hormone-associated mitogen for cultured articular chondrocytes will be elaborated.